Discovery and functional characterization of cardiovascular long noncoding RNAs

Recent advances in sequencing and genomic technologies have resulted in the discovery of thousands of previously unannotated long noncoding RNAs (lncRNAs). However, their function in the cardiovascular system remains elusive. Here we review and discuss considerations for cardiovascular lncRNA discovery, annotation and functional characterization. Although we primarily focus on the heart, the proposed pipeline should foster functional and mechanistic exploration of these transcripts in various cardiovascular pathologies. Moreover, these insights could ultimately lead to novel therapeutic approaches targeting lncRNAs for the amelioration of cardiovascular diseases including heart failure

A simple tool to measure spasticity in spinal cord injury subjects.

This work presents a wearable device and the algorithms for quantitative modelling of joint spasticity and its application in a pilot group of subjects with different levels of spinal cord injury. The device comprises light-weight instrumented handles to measure the interaction force between the subject and the physical therapist performing the tests, EMG sensors and inertial measurement units to measure muscle activity and joint kinematics. Experimental tests included the passive movement of different body segments, where the spasticity was expected, at different velocities. Tonic stretch reflex thresholds and their velocity modulation factor are computed, as a quantitative index of spasticity, by using the kinematics data at the onset of spasm detected through thresholding the EMG data. This technique was applied to two spinal cord injury subjects. The proposed method allowed the analysis of spasticity at muscle and joint levels. The obtained results are in line with the expert diagnosis and qualitative spasticity characterisation on each individual

Impact of processed earwigs and their faeces on the aroma and taste of 'Chasselas' and 'Pinot Noir' wines

The abundance of the European earwig Forficula auricularia L. (Dermaptera, Forficulidae) in European vineyards increased considerably over the last few years. Although earwigs are omnivorous predators that prey on viticultural pests such as grape moths, they are also known to erode berries and to transfer fungal spores. Moreover, they are suspected to affect the human perception of wines both directly by their processing with the grapes and indirectly by the contamination of grape clusters with their faeces. In this study we artificially contaminated grapes with F. auricularia adults and/or their faeces and determined the impact on aroma and taste of white 'Chasselas' and red 'Pinot noir' wines. Whereas the addition of five living adults/kg grapes affected the olfactory sensation of 'Chasselas' wines only marginally, 0.6 gram of earwig faeces/kg grapes had a strong effect on colour, aroma and the general appreciation of 'Chasselas' wines. Faeces-contaminated wines were less fruity and less floral, the aroma was described as faecal and they were judged to be of lower quality. The contamination of 'Pinot noir' grapes with four different densities of living earwig adults (e.g. 0, 5, 10 and 20 individuals/kg grapes) showed that only wines contaminated with more than 10 earwigs/kg grapes smelled and tasted significantly different than the uncontaminated control wine. Earwig-contaminated 'Pinot noir' wines were judged to be of lower quality. The descriptors “animal”, “reductive”, “vegetal”, “acidic”, “bitter” and “tannic” characterised their sensory perception. In conclusion, our results show that there is a real risk of wine contamination by F. auricularia. In particular, earwig faeces and earwig adults at densities above a threshold of 5 to 10 individuals/kg grapes have the potential to reduce the quality of wines. The evolution of earwig populations in vineyards should therefore be monitored carefully in order to anticipate problems during vinification.

A Simple fMRI Compatible Robotic Stimulator to Study the Neural Mechanisms of Touch and Pain.

This paper presents a simple device for the investigation of the human somatosensory system with functional magnetic imaging (fMRI). PC-controlled pneumatic actuation is employed to produce innocuous or noxious mechanical stimulation of the skin. Stimulation patterns are synchronized with fMRI and other relevant physiological measurements like electroencephalographic activity and vital physiological parameters. The system allows adjustable regulation of stimulation parameters and provides consistent patterns of stimulation. A validation experiment demonstrates that the system safely and reliably identifies clusters of functional activity in brain regions involved in the processing of pain. This new device is inexpensive, portable, easy-to-assemble and customizable to suit different experimental requirements. It provides robust and consistent somatosensory stimulation, which is of crucial importance to investigating the mechanisms of pain and its strong connection with the sense of touch

Nonlinear Evolution Equations Invariant Under Schroedinger Group in three-dimensional Space-time

A classification of all possible realizations of the Galilei, Galilei-similitude and Schroedinger Lie algebras in three-dimensional space-time in terms of vector fields under the action of the group of local diffeomorphisms of the space \R^3\times\C is presented. Using this result a variety of general second order evolution equations invariant under the corresponding groups are constructed and their physical significance are discussed

A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion.

The counterregulatory response to hypoglycemia, which restores normal blood glucose levels to ensure sufficient provision of glucose to the brain, is critical for survival. To discover underlying brain regulatory systems, we performed a genetic screen in recombinant inbred mice for quantitative trait loci (QTL) controlling glucagon secretion in response to neuroglucopenia. We identified a QTL on the distal part of chromosome 7 and combined this genetic information with transcriptomic analysis of hypothalami. This revealed Fgf15 as the strongest candidate to control the glucagon response. Fgf15 was expressed by neurons of the dorsomedial hypothalamus and the perifornical area. Intracerebroventricular injection of FGF19, the human ortholog of Fgf15, reduced activation by neuroglucopenia of dorsal vagal complex neurons, of the parasympathetic nerve, and lowered glucagon secretion. In contrast, silencing Fgf15 in the dorsomedial hypothalamus increased neuroglucopenia-induced glucagon secretion. These data identify hypothalamic Fgf15 as a regulator of glucagon secretion

Molecular Biomarkers of Neovascular Age-Related Macular Degeneration With Incomplete Response to Anti-Vascular Endothelial Growth Factor Treatment.

The standard treatment for neovascular age-related macular degeneration (nAMD) consists of intravitreal anti-vascular endothelial growth factors (VEGF). However, for some patients, even maximal anti-VEGF treatment does not entirely suppress exudative activity. The goal of this study was to identify molecular biomarkers in nAMD with incomplete response to anti-VEGF treatment. Aqueous humor (AH) samples were collected from three groups of patients: 17 patients with nAMD responding incompletely to anti-VEGF (18 eyes), 17 patients affected by nAMD with normal treatment response (21 eyes), and 16 control patients without any retinopathy (16 eyes). Proteomic and multiplex analyses were performed on these samples. Proteomic analyses showed that nAMD patients with incomplete anti-VEGF response displayed an increased inflammatory response, complement activation, cytolysis, protein-lipid complex, and vasculature development pathways. Multiplex analyses revealed a significant increase of soluble vascular cell adhesion molecule-1 (sVCAM-1) [ p = 0.001], interleukin-6 (IL-6) [ p = 0.009], bioactive interleukin-12 (IL-12p40) [ p = 0.03], plasminogen activator inhibitor type 1 (PAI-1) [ p = 0.004], and hepatocyte growth factor (HGF) [ p = 0.004] levels in incomplete responders in comparison to normal responders. Interestingly, the same biomarkers showed a high intercorrelation with r2 values between 0.58 and 0.94. In addition, we confirmed by AlphaLISA the increase of sVCAM-1 [ p < 0.0001] and IL-6 [ p = 0.043] in the incomplete responder group. Incomplete responders in nAMD are associated with activated angiogenic and inflammatory pathways. The residual exudative activity of nAMD despite maximal anti-VEGF treatment may be related to both angiogenic and inflammatory responses requiring specific adjuvant therapy. Data are available via ProteomeXchange with identifier PXD02247

Blind source separation aided characterization of the γ′ strengthening phase in an advanced nickel-based superalloy by spectroscopic 4D electron microscopy

The γ’ strengthening phase in an advanced nickel-based superalloy, ATI 718Plus, was characterized using a blind source separation applied to a four dimensional X-ray microanalysis dataset obtained by scanning transmission electron microscopy. Selected patterns in the X-ray spectra identified by independent component analysis were found to be spatially and chemically representative of the matrix (γ) and precipitate phases (γ’) present in the superalloy, enabling their size, shape and distribution to be determined. The three dimensional chemical reconstruction of the microstructure may provide insight into the role of the various alloying elements in the evolution of the microstructure at the nano-scale.The research leading to these results has received funding from the European Union Seventh Framework Programme under Grant Agreement 312483 - ESTEEM2 (Integrated Infrastructure Initiative-I3), as well as from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC grant agreement 291522 - 3DIMAGE. D.R. acknowledges support from the Royal Society’s Newton International Fellowship scheme. RKL acknowledges a Junior Research Fellowship at Clare College. RK acknowledges financial support from Rolls-Royce, EPSRC and the BMWi under EP/H022309/1, EP/H500375/1 and grant number 20T0813. F.d.l.P. and C.D. acknowledge 26 funding from the ERC under grant no. 259619 PHOTO EM. Special thanks to Giorgio Divitini and Lech Staniewicz for preparation of the FIB needle specimen and to Stephen A Croxall for SEM/FIB imaging.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.actamat.2016.01.04

Conformal Properties of Chern-Simons Vortices in External Fields

The construction and the symmetries of Chern-Simons vortices in harmonic and uniform magnetic force backgrounds found by Ezawa, Hotta and Iwazaki, and by Jackiw and Pi are generalized using the non-relativistic Kaluza-Klein-type framework presented in our previous paper. All Schrodinger-symmetric backgrounds are determined.Comment: 10 pages,CPT-94/p.3028, te